anti-claudin 18.2 antibody-drug conjugate SKB315

An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against the tumor-associated antigen (TAA) claudin 18.2 (CLDN18.2; A2 isoform of claudin-18) that is site-specifically conjugated, via a stable linker, to a cytotoxic DNA topoisomerase I (Top I) inhibitor, with potential antineoplastic activity. Upon administration of anti-CLDN18.2 ADC MK-1200, the antibody moiety specifically targets and binds to CLDN18.2 expressed on tumor cells. Upon internalization and the release of the Top I inhibitor, the Top I inhibitor targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication and apoptosis in CLDN18.2-expressing tumor cells. CLDN18.2, a tight junction protein and stomach-specific isoform of claudin-18, is expressed on a variety of tumor cells. Its expression in healthy tissues is strictly confined to short-lived differentiated epithelial cells of the gastric mucosa.